| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HR-positive, HER2-negative advanced breast cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10027475 |
| E.1.2 | Term | Metastatic breast cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10070575 |
| E.1.2 | Term | Estrogen receptor positive breast cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10072737 |
| E.1.2 | Term | Advanced breast cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10073289 |
| E.1.2 | Term | Premenopausal breast cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to determine whether the overall response rate (ORR) in the experimental arm (400 mg) is non-inferior to the control arm (600 mg) based on local tumor assessments (RECIST version1.1) for all patients that have been treated for at least 6 months or have discontinued the study treatment. |
|
| E.2.2 | Secondary objectives of the trial |
Key secondary objective is to evaluate QTc (with Fridericia's correction) prolongation in the experimental arm.
Other secondary objectives include safety and tolerability, progression-free survival, clinical benefit rate, time to response, duration of response, pharmacokinetics of ribociclib when given in combination with NSAI.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Patient has advanced (loco-regionally recurrent or metastatic) breast cancer not amenable to curative therapy.
• Patient has a histologically and/or cytologically confirmed diagnosis of ER-positive and/or PgR-positive breast cancer based on the most recently analyzed tissue sample, and all tested by local laboratory.
• Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample.
• Patient must have measurable disease, i.e., at least one measurable lesion according to RECIST version 1.1. (a lesion in a previously irradiated site may only be counted as a target lesion if there is clear evidence of progression since the irradiation).
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by the central laboratory:
- QTcF interval at screening < 450 ms (QT interval using Fridericia's correction)
- Mean resting heart rate 50 to 90 bpm (determined from the ECG)
• Women of childbearing potential (CBP), defined as all women physiologically capable of becoming pregnant, must have confirmed negative serum pregnancy test (for β- hCG) within 14 days prior to randomization.
• Women of CBP must be willing to use highly effective methods of contraception.
Please refer to Section 5.1 of the protocol for full details on inclusion criteria. |
|
| E.4 | Principal exclusion criteria |
• Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's judgment.
• Patient who received any prior systemic anti-cancer therapy (including endocrine therapy, chemotherapy, prior CDK4/6 inhibitors) for aBC. Patients who received neo-/adjuvant therapy for breast cancer are eligible.
• Patient is concurrently using other anti-cancer therapy.
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major toxicities.
• Patient has received extended-field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to randomization, and has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
• Patient has a concurrent malignancy or malignancy within 3 years of the randomization date, with the exception of adequately treated basal or squamous cell skin carcinoma, or curatively resected cervical carcinoma in situ.
• Patients with central nervous system (CNS) involvement unless they meet specific stability criteria.
• Patient has clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.
• Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, and has not fully recovered from side effects of such treatment.
Please refer to Section 5.2 of the protocol for details on exclusion criteria. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall response rate (ORR). ORR is based on local tumor assessments (RECIST version 1.1) for all patients that have been treated for at least 6 months or have discontinued the study treatment. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| After all patients have been treated for 6 months or have discontinued study treatment. |
|
| E.5.2 | Secondary end point(s) |
-Δ QTcF at Cycle 1 Day 15 (at 2h post-dose) (Key Secondary Endpoint)
-Progression-free survival (PFS)
-Clinical benefit rate (CBR)
-Time to response (TTR)
-Duration of response (DOR)
-Pharmacokinetics (PK) of ribociclib: Cmax
-Pharmacokinetics (PK) of ribociclib: Tmax
-Pharmacokinetics (PK) of ribociclib: AUC0 - 24h
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| After all patients have been treated for 6 months or have discontinued study treatment. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 49 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Brazil |
| Canada |
| Colombia |
| Costa Rica |
| India |
| Jordan |
| Peru |
| South Africa |
| Thailand |
| United States |
| Austria |
| Finland |
| France |
| Lithuania |
| Sweden |
| Bulgaria |
| Czechia |
| Germany |
| Belgium |
| Hungary |
| Portugal |
| Russian Federation |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of study will be declared as the earliest occurrence of one of the following:
-All patients have died or discontinued from the study or have been followed up for approximately 3 years from randomization.
-Patients who in the opinion of the investigator are still deriving clinical benefit in this study can continue provision of study treatment through an alternative setting.
-Another clinical study becomes available that can continue to provide ribociclib in this patient population |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
